The effects of dihydrochandonium and other chandonium analogues on neuromuscular and autonomic transmission.

Abstract

Abstract The muscle relaxant chandonium and four of its analogues have been assessed for neuromuscular, ganglion blocking and vagolytic activity in the chloralose-anaesthetized cat, for neuromuscular blocking activity in the chick isolated biventer cervicis and rat phrenic nerve-hemidiaphragm preparations, for muscarinic and histamine blocking activity in the guinea-pig isolated ileum preparation and for effects on adrenergic responses in the rat isolated vas deferens preparation. All five compounds produced neuromuscular block of rapid onset and short duration when given to cats in doses of 5–500 μg kg−1 and produced non-depolarizing competitive neuromuscular blockade in the isolated skeletal muscle preparations. Saturation of the 5–6 androstene bond to produce dihydrochandonium (HS692) resulted in a loss of potency by a factor of 0·5. The NN-diethyl analogue of dihydrochandonium (HS693) was about half as potent as HS692. The triethyl (HS704) and NN-diethyl (HS705) analogues of chandonium possessed one-tenth and one-fifth respectively of the muscle relaxant activity of chandonium. In cats, all compounds inhibited the bradycardia produced by vagal stimulation and by methacholine, the vagolytic effect of HS693 being particularly powerful and long-lasting. Although the compounds did not block the depressor response to methacholine in vivo, all the compounds inhibited responses to carbachol in the guinea-pig isolated ileum. However, from pA2 values the compounds were found to be 10–100 times more active at nicotinic than at muscarinic receptors. None of the compounds had histamine-blocking activity, ganglion-blocking activity, or actions on adrenergic responses.